Inflammation is one of the commonest causes of human and animal disability. It plays a major role in diseases such as rheumatoid arthritis, osteoarthritis, gout and ankylosing spondylitis: in reactions to infections of all types, to trauma, and to some cancers; in inflammatory conditions of all organs examples being pancreatitis, myocarditis, dermatitis and pneumonitis; in dysmenorrhoea; and possibly in reactions of blood vessel walls in cardiovascular disease. Recently it has been suggested that dementia also has a major inflammatory component (Rogers J. et al, Neurobiology 43: 1609-1611, 1993). Inflammation is in many situations a normal and desirable response on the part of the body which is directed at bringing a disease process under control. However, in other situations including the various forms of arthritis and the dementias, the inflammation may be excessive and prolonged, so contributing to rather than preventing the damage. In these situations anti-inflammatory drugs may be used to control the inflammation and relieve the symptoms, particularly the pain which can result.
Anti-inflammatory drugs tall into two broad categories, the steroids and the non-steroidal anti-inflammatory drugs (NSAIDs). This specification is concerned with the NSAIDs, many of which act at least in part by blocking the conversion of essential fatty acids (EFAs) to prostaglandins, leukotrienes and other substances generally known as eicosanoids. However, many other facets to the anti-inflammatory and analgesic actions of these drugs have been described and it is unlikely that a single mechanism of action can account for all their effects.
The NSAIDs used as anti-inflammatories and analgesics fall into several broad categories.
1. The salicylates and various derivatives thereof, including acetyl salicylic acid, salicylic acid, methyl salicylate, diflunisal and salsalate.
2. The pyrazolone derivatives, including phenylbutazone, oxyphenbutazone, antipyrine, aminopyrine, dipyrone and apazone.
3. The para-aminophenol derivatives, including acetaminophen (paracetamol), phenacetin and related compounds.
4. Indomethacin, sulindac and related compounds.
5. The fenamates, including; mefenamic, meclofenamic, flufenamic, tolfenamic, and etofenamic acids, and related compounds.
6. The proprionic acid derivatives including ibuprofen, naproxen, fenoprofen, ketoprofen, flurbiprofen and related compounds.
7. The oxicam derivatives such as piroxicam and related compounds.
8. The phenylacetic acid derivatives such as diclofenac and related compounds.
9. Other NSAIDs such as tolmetin, etodolac and nabumetone.
While the NSAIDs have proved extremely valuable in the management of symptoms, they all have two major drawbacks:
1. The control of inflammation is rarely complete and the underlying inflammatory process usually proceeds in spite of drug treatment.
2. All have important side effects, although these vary in severity from drug to drug. The gastro-intestinal tract and the kidneys are particularly likely to be damaged, although adverse effects on almost every tissue have been noted with central nervous system side effects being particularly common with some drugs.